Performance of the CMS High Granularity Calorimeter prototype to charged pion beams of 20−-300 GeV/c

The upgrade of the CMS experiment for the high luminosity operation of the LHC comprises the replacement of the current endcap calorimeter by a high granularity sampling calorimeter (HGCAL). The electromagnetic section of the HGCAL is based on silicon sensors interspersed between lead and copper (or copper tungsten) absorbers. The hadronic section uses layers of stainless steel as an absorbing medium and silicon sensors as an active medium in the regions of high radiation exposure, and scintillator tiles directly readout by silicon photomultipliers in the remaining regions. As part of the development of the detector and its readout electronic components, a section of a silicon-based HGCAL prototype detector along with a section of the CALICE AHCAL prototype was exposed to muons, electrons and charged pions in beam test experiments at the H2 beamline at the CERN SPS in October 2018. The AHCAL uses the same technology as foreseen for the HGCAL but with much finer longitudinal segmentation. The performance of the calorimeters in terms of energy response and resolution, longitudinal and transverse shower profiles is studied using negatively charged pions, and is compared to GEANT4 predictions. This is the first report summarizing results of hadronic showers measured by the HGCAL prototype using beam test data.Comment: To be submitted to JINS

Non-radiolabelled PCR consensus primers and automatic sequencing enable rapid identification of tumor-specific V(H) CDR3 in aggressive B-cell malignancies.

Even though the results of current therapy are improved for B-cell acute lymphoblastic leukemia (B-ALL) and Burkitt's lymphoma (BL), prognosis of relapsed mature B-ALL and BL still remain extremely poor. In this study, we investigated the possibility of applying the use of non-radiolabelled PCR consensus primers and automatic sequencing for the rapid identification of the tumor-specific V(H) CDR3 nucleotide sequence, in mature B-ALL and BL. RNA was extracted from four consecutive, unselected samples from BL cases and three consecutive, unselected samples from mature B-ALL cases. The feasibility of the identification of the tumor-specific V(H) CDR3 nucleotide sequence was then assessed by using non-radiolabelled PCR consensus primers with automatic sequencing. The tumor-specific V(H) CDR3 nucleotide sequence was successfully identified for all seven patients (3 mature B-ALL and BL). The time required was substantially lower than that of the other methods previously published, despite the poor quality of some of the samples. The procedure showed rapidity, reliability and reproducibility. The characteristics of the methodology applied widen the possibility of developing anti-idiotypic therapeutic strategies, even in these B-cell malignancies

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D–induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D–neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada’s Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.

Schistosomiasis is a disease caused by parasitic flatworms of the Schistosoma spp., and is increasingly recognized to alter the immune system, and the potential to respond to vaccines. The impact of endemic infections on protective immunity is critical to inform vaccination strategies globally. We assessed the influence of Schistosoma mansoni worm burden on multiple host vaccine-related immune parameters in a Ugandan fishing cohort (n = 75) given three doses of a Hepatitis B (HepB) vaccine at baseline and multiple timepoints post-vaccination. We observed distinct differences in immune responses in instances of higher worm burden, compared to low worm burden or non-infected. Concentrations of pre-vaccination serum schistosome-specific circulating anodic antigen (CAA), linked to worm burden, showed a significant bimodal distribution associated with HepB titers, which was lower in individuals with higher CAA values at month 7 post-vaccination (M7). Comparative chemokine/cytokine responses revealed significant upregulation of CCL19, CXCL9 and CCL17 known to be involved in T cell activation and recruitment, in higher CAA individuals, and CCL17 correlated negatively with HepB titers at month 12 post-vaccination. We show that HepB-specific CD4+ T cell memory responses correlated positively with HepB titers at M7. We further established that those participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination, but higher regulatory T cells (Tregs) post-vaccination, suggesting changes in the immune microenvironment in high CAA could favor Treg recruitment and activation. Additionally, we found that changes in the levels of innate-related cytokines/chemokines CXCL10, IL-1β, and CCL26, involved in driving T helper responses, were associated with increasing CAA concentration. This study provides further insight on pre-vaccination host responses to Schistosoma worm burden which will support our understanding of vaccine responses altered by pathogenic host immune mechanisms and memory function and explain abrogated vaccine responses in communities with endemic infections

Using graph neural networks to reconstruct charged pion showers in the CMS High Granularity Calorimeter

International audienceA novel method to reconstruct the energy of hadronic showers in the CMS High Granularity Calorimeter (HGCAL) is presented. The HGCAL is a sampling calorimeter with very fine transverse and longitudinal granularity. The active media are silicon sensors and scintillator tiles readout by SiPMs and the absorbers are a combination of lead and Cu/CuW in the electromagnetic section, and steel in the hadronic section. The shower reconstruction method is based on graph neural networks and it makes use of a dynamic reduction network architecture. It is shown that the algorithm is able to capture and mitigate the main effects that normally hinder the reconstruction of hadronic showers using classical reconstruction methods, by compensating for fluctuations in the multiplicity, energy, and spatial distributions of the shower's constituents. The performance of the algorithm is evaluated using test beam data collected in 2018 prototype of the CMS HGCAL accompanied by a section of the CALICE AHCAL prototype. The capability of the method to mitigate the impact of energy leakage from the calorimeter is also demonstrated

Neutron irradiation and electrical characterisation of the first 8” silicon pad sensor prototypes for the CMS calorimeter endcap upgrade

International audienceAs part of its HL-LHC upgrade program, the CMS collaboration is replacing its existing endcap calorimeters with a high-granularity calorimeter (CE). The new calorimeter is a sampling calorimeter with unprecedented transverse and longitudinal readout for both electromagnetic and hadronic compartments. Due to its compactness, intrinsic time resolution, and radiation hardness, silicon has been chosen as active material for the regions exposed to higher radiation levels. The silicon sensors are fabricated as 20 cm (8”) wide hexagonal wafers and are segmented into several hundred pads which are read out individually. As part of the sensor qualification strategy, 8” sensor irradiation with neutrons has been conducted at the Rhode Island Nuclear Science Center (RINSC) and followed by their electrical characterisation in 2020-21. The completion of this important milestone in the CE's R&D program is documented in this paper and it provides detailed account of the associated infrastructure and procedures.The results on the electrical properties of the irradiated CE silicon sensors are presented